Mutant mice: From muscular to Methuselah, they're on rise

SAN FRANCISCO - They're bred by the millions, the mutants, created to carry the ghastliest of diseases for the benefit of the human race.

Since researchers published the mouse's entire genetic makeup in map form three years ago, increasingly exotic rodents are being created with relative ease.

There's the Schwarzenegger mouse - injected with muscle-building genes. The marathon mouse, which never seems to tire. Researchers recently engineered some mice to be extremely addicted to nicotine, and others to be immune to scrapie, a close cousin to the brain-wasting mad cow disease. And scientists are in hot pursuit of a Methuselah mouse, able to cheat death long after its natural brethren meet their maker.

Millions of these and other mutant mice are routinely created now, by injecting disease-causing genes or "knocking out" genes in mouse embryos. Their decreasing cost and increasing availability is helping researchers in pursuit of disease cures.

Researchers first genetically engineered a mouse in 1980. But until recently, such creations were mostly scientific novelties.

That changed after former President Bill Clinton announced the mapping of the human genome in 2000. That's because mice and men are nearly genetically identical, each possessing just a few hundred different genes out of a possible 25,000. Mice have become powerful, living research tools.

Nearly all the genetically engineered mice in circulation today have but one gene added, subtracted or altered. The problem with that model is that many diseases such as diabetes and cancer are caused by multiple gene malfunctions.

"Eventually, that's where engineered mice are going," said Mendell Rimer, a University of Texas neuroscientist who tends to about 500 mice in his Austin lab. "That's a more realistic disease model."

Rimer's genetically engineered mice are among the most advanced, and offer a glimpse of the breakthroughs to come.

He spent 2 1/2 years engineering mice with muscles that lose connection to their nerve cells. But he's also taken his work one step further; Rimer is able to turn on the mutant gene by feeding the genetically engineered mouse an antibiotic.

"We can control the timing of the defect that we induce in these mice," Rimer said. "This type of complexity is where genetic engineering is heading."